XOTES 2539
Vol. $3, No. 6,Jun.e 1968 a triplet at T 6.67.lS The fluorine nmr spectrum of I11 shows peaks for six different fluorines grouped roughly in pairs a t 107, 113, 120, 122, 131, and 133 ppm upfield from internal fluorotrichloromethane. These chemical shifts seem inconsistent with any structure containing the valence-tautomeric bicyclo[4.2.0] systemi1 and I11 is preferred, although the structure cannot be regarded as unequivocably proved.
Electron-Transfer Polymers. XXXIII. Compounds Related to Tocopherol NOBUONAKADAYASHI, GERH.4RD AND
Sterling Chemistry Laboratory, Yale Cniversity, New Haued, Connecticut 06620 Received January
I
H
A mechanism for the conversion of I into I11 can be constructed and involves a carbon-carbon bond shift (possibly in the norcaradiene form 11) followed by a hydrogen shift. These steps have rather good analogy, albeit in much more simple systems.i6-is Experimental Section Spiro[4.6] -6,7,8,9,10,1 l-hexafluoroundeca-l,3,6,8,lO-pentaene (I).-A solution of I ml of diazocyclopentadiene1~~20 in 122 g of hexafluorobenzene was irradiated through a Pyrex filter with a 450-VIT Hanovia medirim-pressure mercury arc for 14 hr. The hexafluorobenzeiie was removed by distillation a t 0.1 mm leaving a dark brown, thick oil. This was distilled in a bulb-to-bulb apparatus a t room temperature and 0.025 mm to yield 500 mg of a yellow oil, Spectral analysis revealed this to be I contaminated with traces of dicycloperitadiene. AnaZ.21 Calcd for CIIH~FB:C, 52.82; H, 1.61. Found: C, 53.01; H, 1.72. Pyrolysis of I. A . Flow System.--A solution of 10 mg of I in 0.5 ml of cyclohexane was dropped slowly into a 12-in. Pyrex tube packed with glass helices under nitrogen a t 220'. Residence time wab ea. 1 scc. Urider these coiiditions I is converted into a mixtiire of 407, I and 6 0 7 I11 with ea. 90% recovery. Incrensing the temperature to 255' resulted in 90-959; conversion into I11 with somewhat reduced recovery. B. Gas Chromatography.-Compound I is easily converted into I11 in the injector or detector-collector of R gas chromatograph. The peak corresponding to I ib simply collected and reinjected. Injection on a 5-ft SE 30 silicone oil column operated a t 95" (injector, 130", and detector, 210") with a flow rate of 100 cc of helium/min results, as revealed by reinjection, in ca. 25% I (retention time 22 min) and 757* I11 (retention time 42 min, mp 50-52'). AnaE. Found: C , 52.71; H, 1.66.
Registry No.-I, 16033-88-5; 111, 16021-17-3; diazocyclopentadiene, 1192-27-4; hexafluorobenzene, 39256-3. (15) N. S. Bhacca, L. F. Johnson, and J. N. Shoolery, "Varian N M R Spectra Catalog," Varian Associates, Palo Alto, Calif., 1962, No. 227. (16) J. W.D e H a a n and H. Kloosterziel, Rec. Trav. Chim. Pays-Bas, 84, 1594 (19651, and references therein. (17) W . R. Roth, Tetrahedron Lett., 1009 (1964). (18) S. McLean a n d R. Haynes, ibid., 2385 (1964). (19) W. von E. Doering and C. H . DePuy, J . Amer. Chem. Soc., 75, 5955 (1953). (20) T. Weil, J. Ore. Chem., 28, 2472 (1963). (21) Although acceptable carbon a n d hydrogen analyses could be obtained on I, fluorine analysis was poor. We do not know the precise cause of this b u t can point out that I is most unstable. Exposure t o air results in rapid darkening and eventual deposition of a brown-black solid.
JTEGNER,
HAROLD G. CASSIDY
4, 1968
Redox polymersi&have been prepared by polycondensation of 2,5-disubstituted benzoquinones.'b I n the resulting linear polymers the redox group is part of the chain. In this paper we report the preparation of redox monomer from a quinonyl glycol. In this polymer the redox groups are pendant from the chaina2 In the course of preparing this monomer several interesting new compounds, analogs of tocopherol derivatives, were prepared, and new behaviors were observed. Trimethylhydroquinone (1,3,4-trimethyl- 2,5-dihydroxybenzene) was converted into 3-hydroxy-6-methoxy-2,4,5-trimethylbenzyl chloride (I).3 Treatment with sodioethyl malonate produced ethyl(3-hydroxy6-met hoxy-2,4,5-t rimethy1b enzy1)malonate (II). Reduction of I1 with lithium aluminum hydride yielded 2-(3'-hydroxy-6'-methoxy-2',4'-5'-trimethyl benzy1)propane-1,3-diol (111). (See Chart I.) Oxidative cleavage of the methoxy group in I11 with lead tetraacetate suspended in 50% aqueous tetrahydrofuran (THF) produces the desired monomer, 2-(duroquinonyl)propane-1,3-diol (V), as yellon- crystalline material. If, however, 111 is oxidized with lead tetraacetate suspended in dry T H F there is produced a white, crystalline material with a carbonyl band at 1683 cni-', and no hydroxyl band in the ir spectrum and A,, at 2-14 mp ( E 1.09 X lo4) in the uv spectrum. The uv spectrum closely resembles that of 9-substituted oc-to~opherol.~ This new substance appeared to be Sa,3-epoxymethano5,7,8- trimethyl - 6H,8aH-dihydrochronian- 6-one (IV), Then IV, shaken with cation exchange resin in the acid form in 50% aqueous THF, gives IT in good yield. Reduction of IV in the presence of palladium charcoal yields 3 - hydroxymethyl- 5,7,S- trimethylchroman- 6-01 (1'11) quantitatively. Reoxidation of VI1 produces IV by using ceric ammonium nitrate or silver oxide in dry T H F quantitatively. When yellow V is reduced in an attempt to obtain 2-(durohydroquiny1)propane1,3-diol (VI), a white crystalline material could be isolated but in air it quickly oxidizes to red (quinhydrone!) then yellow quinone V. If the reduction is carried out in acid, there is obtained stable VII, presumably via VI. When the methoxy group of I11 is cleaved with HCl, there is formed VII, presumably via the VI pathway (Chart I). These behaviors bear strong analogy to those of the tocopherols. Structure VI1 differs from a-tocopherol only in the substituents on the oxygen ring. When the corresponding ring is opened there is (1) (a) H. G. Cassidy and K. A. Kun, "Oxidation-Reduction Polymers," Interscience Publishers, Inc., New York, N. Y., 1965; (b) G. U'egner, N. Naksbayashi, a n d H. G. Cassidy, J . Ore. Chem., 32, 3155 (1967). (2) Syntheses and properties of the polymers will be published elsewhere. (3) W. John and F. H. Rathmann, Ber., 74, 890 (1941). (4) W. H. Harrison, J. E. Gander, E. R . Blakley, and P. D. Boyer, Biochim. Biophys. Acta, 21, 150 (1956).
The Journal of Organic Chemistry
2540 NOTES
CH3
w
Iv
Preparation of 11.-To a sodium ethylate solution i6.10 g (0.265 g-atom) of sodium in 135 ml absolute ethanol] was added 23.2 g (0.145 mol) of ethyl malonate in 40 ml of absolute ethanol, dropwise with cooling. After 15 min, 28.2 g (0.131 mol) of I in 100 ml of dry T H F was added slowly. The reaction mixture was refluxed 1.5 hr. Refluxing longer than 2 hr decreased the yield. After neutralization with acetic acid, the solvent was
removed and the residue was suspended in water and extracted with ether. The ether solution was dried with magnesium sulfate, the solvent was removed, and the residue was crystallized from carbon tetrachloride (refrigerator) to yield 13.9 g (31 -4%) of white crystals: mp 118-119’; ir spectrum, OH (3475), C=O (1750, 1725), -CO- (1250 ern-’); nmr,’ CHs (ring) and CH a t 7 7.90 and 7.84 (10) and OI-CHZ a t 6.80 (2), CzHs (ester) a t 8.81 (6) and 5.88 (4) CH3-0- a t 6.38 (3). Anal. Calcd for C1,HzeOs: C, 63.88; H , 7.75. Found: C, 63.90; H, 7.68. When the synthesis was carried out with 1.20 g (0.052 g-atom) of sodium, 8.0 g (0.050 mol) of ethyl malonate, and 10.7 g (0.050 mol) of I, a yield of 5.3 g (31%) of I1 was obtained. Preparation of 111.-To a stirred suspension of 1.2 g of lithium aluminum hydride in 50 ml of dry THF, cooled in ice, was added dropwise 50 ml of T H F containing 5.5 g (0.0162 mol) of 11. After the vigorous reaction had subsided the mixture was refluxed for 2 hr. Excess hydride was removed by careful addition of water, and the mixture was neutralized with acetic acid. Saturated aqueous ammonium chloride solution was added, and the upper, organic layer was decanted. The water layer was washed with ether, and the washings and organic layer were combined and dried with magnesium sulfate. The solvent was removed by evaporation from the dried mixture, and the residue
(5) J. Bunyan, D. McHale, and J. Green, Brit. J. Xutr., 17, 391 (1963). (6)J. Green and D. McHale in “Biochemistry of Quinones,” R . A. Morton, Ed., Academic Press Inc., New York, N . Y., 1965, Chapter 8.
(7) Nmr data were obtained with a Varian Associates Model A-60 spectrometer. The chemical shifts are given in r values; the numbers within parentheses indicate the number of protons.
obtained the unstable hydroquinone which is readily oxidized to a-tocopherolquinone (IX) .5t6 The intriguing correspondence of IV, V, VI, and VI1 to 9-substituted-a-tocopherone, a-tocopherolquinone (IX) , a-tocopherolhydroquinone, and a-tocopherol (VIII)496leads us to point out the important role of the y-hydroxyl. The redox potential of durohydroquinone is low; the hydroquinone form is very easily oxidized. By building into the molecule a suitably placed hydroxyl we provide automatic stabilization of the reduced form (VII) through ring closure. Experimental Section
Vol. 33, No. 6 , June 1968 was recrystallized from methanol to give 2.55 g (61.5y0) of white crystals: mp 173-175'; ir, OH (3415, 3308), -C-0 (1240, 1167, and 1036 cm-I); nmr,' CHI (ring) and CH a t T 8.03, 7.88, 7.71 (total lo), a-CH2 a t 7.23 (2), CHIO a t 6.63 (3), -CH20- a t 6.17 (4). Anal. Calcd for C14H~Z04: C, 66.11; H , 8.72. Found: C, 65.72; H, 8.57. Preparation of IV and V. A.-To a stirred solution of 0.62 g (0.0024 mol) of I11 in 20 ml of dry T H F was added 1.2 g (0.0027 mol) of lead tetraacetate. The suspension was refluxed 15 min. Aqueous sodium hydroxide was added and the mixture was extracted with ether. On evaporation of the solvent from the dried ether solution there was obtained a red-yellow oily residue. This was dissolved in a small amount of acetonitrile and refrigerated. White plates crystallized in a yield of 0.15 g (28y0), mp 159-160'. From the mother liquor, by recrystallization from THF-n-heptane a further yield of 0.13 g (237,) of white crystals, mp 159-160", was obtained, and 0.07 g (12%) of yellow crystals melting a t 79-79.5" were also obtained. The white crystalline material is 1'; and the yellow is 5'. Anal. Calcd for C13H1603 (117): C, 70.89; H , 7.32. Found: C, 71.02; H , 7.28. Calcd for ClnHlsOl (V): C, 65.53; H, 7.61. Found: C, 65.46; H , 7.58. The ir spectrum of IV showed C=O a t 1683, 1644, and 1633 (C=C) and -C-0- at 1260, 1197, 1099, and 1040. That for V showed -OH :tt 3285; C = O (quinone) a t 1630; and -CO- a t 1303, 1260, and 1070 cm-1. The nmr spectra' of IV showed CHa (ring) and CH2 a t 8.00 (3), 8.14 (6), and 7.77 (1); a-CHz a t 7.24 (2); -CH2-0 a t 6.06, 5.91, 5.72, and 5.58 (total 4). B.-To 22.0 g (0.0866 mol) of I11 in 700 ml of T H F was added 700 ml of water, then 44.0 g (0.995 mol) of lead tetraacetate. The suspension was stirred and refluxed for 30 min. After addition of sodium hydroxide, extraction with ether, and drying and evaporation of the ether, there was obtained a red-yellow residue. This was dissolved in a small amount of THF, and n-heptane was added. Compound V crystallized. The crude material was recrystallized from THF-n-heptane to yield 11.0 g (63.4%), mp 79.0-79.5'. From the mother liquor there was obtained 2.0 g (10.5%) of IV. Preparation of VII. A.-A suspension of 1.0 g (0.0039 mol) of I11 in 30 ml of water and 30 ml of concentrated hydrochloric acid was refluxed, with stirring, for 9.5 hr. On cooling, the product crystallized. ltecrystallization from acetonitrile gave 0.62 g (72%) of 1-11 as white crystals: mp 171-172'; ir spectrum, OH [3300, 3150, (chromanol, 1610)] and -C-0- (1255, 1241, 1125 em-'); ninr," CH, (ring) and CH a t 8.29, 8.25, 8.17, (total lo), CH2 a t 7.92 (2), -CHzO- a t 6.69 ( 2 ) , and 6.43 (2). Anal. Calcd for C13H1803: C, 70.23; H , 8.16. Found: C, 70.06; H , 8.09. B.-A solution of 0.50 g (0.0023 mol) of I V in 20 ml of T H F was shaken in an atmosphere of hydrogen with a catalytic amount of 10% palladium charcoal at room temperature. Within 10 min 60 cc of hydrogen was absorbed (theory, 51 cc; probably the excess went to the solvent.) From the filtered solution there was obtained a pale yellow powder which on recrystallization from acetonitrile, yielded 0.40 g (80%) of white crytals, mp 171-172'. No depression was observed in mixture melting point with VII. C.-A solution of 0.5 g (0.0021 mol) of V in 5 ml of glacial acetic acid and 15 ml of water was refluxed with 0.5 g of zinc powder for 0.5 hr. The mixture was neutralized with sodium hydroxide, extracted with ether, and the extract was dried and evaporated. The reddish residue was recryst,allized from acetonitrile to give 0.28 g (60%) of VII, mp 171-172'. Oxidative titration of VI1 with ceric ammonium nitrate in 90% aqueous acetic acid a t 25' gave an equivalent weight of 114.5 (calcd, 111). The midpoint potential was about 0.657 V. Ultraviolet Spectra.--The solvent, Amex in mfi, and the molar extinction coefficient are given in that order: IT' (CHZCL, 244, 1.09 X 104); V (CH,Cl,, 272, 1.65 X lo4; CH30H, 269, 1.99 X lo4); VI (CH,OH, 289, 3.9 x 105); VI1 (CH2C12, 296, 2.29 x 103).
Registry No.-11, 16526-47-9; 111, 16526-48-0; IV, 16526-49-1; Y, 16526-50-4; VII, 16526-51-5; VIII, 16526-52-6. Acknowledgment.-We thank Mrs. Irmlind Stronkowski for technical assistance. The work was sup-
XOTES 2541 ported by Research Grant Gh!t 10864 from the Research Grants Branch, National Institute of General Medical Sciences, U. S. Public Health Service, for which we express our thanks.
Reaction of Pseudoxazolones and Hydrazoic Acid YOSHIOIWAKURA, FUJIO TODA, AND YOSHINORI TORII Department of Synthetic Chemistry, Faculty of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo, Japan Received December 6. 1967
The reaction of 4-arylidene-5-oxazolones with hydrazoic acid was reported by Awad, et al.'J to produce tetrazolylacrylic acid derivatives in good yields. In examining the reactivity of 2-isopropylidene-4-methyl3-oxazolin-5-one3 (Ia, pseudooxazolone) with more than 2 mol of hydrazoic acid, we obtained white crystalline materials in 38% yield by their reaction condition as shown in Table I. COOH
ArCH=C-N I II O=C,o,C-R
NaNs,H20
AcoH
Ar CHIC-N,
*
C=N I
R
TABLE I ELEMENTAL ANALYSES OF IV R Me
CPr i-Bu a
Mp, 'C 210* 216O 216a
Crude yield,
% 38 71 96
%--
----Calcd,
C
H
N
42.40 6.56 38.10 48.10 7.60 33.00 5 0 . 5 0 8 . 0 1 30.90
,---Found, C 42.77 48.59 50.71
yo---H N 6 . 6 1 37.81 7 . 5 5 32.18 7 . 9 4 30.95
Melted with decomposition.
That this product was a urea derivative was established by several spectral methods. The infrared spectrum showed strong absorptions at 3310, 2140,4 and 1660 cm-' arising from amide and urea E-H stretching, azide asymmetric stretching, and amide and urea carbonyl stretching vibrations, respectively. The nmr spectrum of the product displayed a 12-proton singlet a t 6 1.44 due to four gem-methyl groups, a &proton doublet centered a t 1.47; a 2-proton quartet centered a t 5.65 ( J = 6 cps) ; and a broad N H proton singlet at 3.66 in pyridine. Mass spectra of IV offered a good indication of the presence of azide linkages and of the structure of IV. Each peak corresponded well to fragments formed from the molecular ion peak by cleavage at positions as shown in Chart I. In addition, elimination of methyl and isobutyl radicals gave rise to m/e 353 and 395 in IVa and IVc , respectively . The first step in this transformation is postulated to be 1,4 addition of hydrazoic acid to I forming a satu(1) W. 1. Awad, A. F. M. Fahmy, and 8 . M. A. Sammour, J . 0 ~ g Chem., . SO, 2222 (1965). (2) H. Behringer and W. Grimme, Chem. Ber., 92, 2967 (1959). (3) Y. Iwakura, F. Toda, and Y. Torii, Tetrahedron, 22, 3363 (1967). (4) C. N. R . Rao, T. S. Chao, and C. W. W. Hoffman, Anal. Chem., 29, 916 (1957).
